Civil Aerospace Medical Institute

OBJECTIVE: To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). METHODS: Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score >/=4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. RESULTS: Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer >/=1:80 and/or anti-double-stranded DNA [anti-dsDNA] >/=30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician's global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. CONCLUSION: Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.

Increasing evidence indicates widespread occurrence of pharmaceuticals and personal care products (PPCPs) in municipal effluent discharges and surface waters. Studies that characterize the fate and effects of PPCPs in aquatic systems are limited, and to our knowledge, data regarding pharmaceutical accumulation in fish of effluent-dominated ecosystems have not been previously reported. In the present study, fish populations were sampled from a reference stream and an effluent-dominated stream in north Texas, USA. Lepomis macrochirus, Ictalurus punctatus, Cyprinus carpio, and Pomoxis nigromaculatus were killed; the liver, brain, and lateral filet tissues dissected; and the tissues stored at -80 degrees C until analysis. Fish tissues were extracted using solid-phase extraction and then analyzed by gas chromatography-mass spectrometry in the negative chemical ionization mode. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and the SSRI metabolites norfluoxetine and desmethylsertraline were detected at levels greater than 0.1 ng/g in all tissues examined from fish residing in a municipal effluent-dominated stream. To our knowledge, the present study is the first report of SSRI residues in fish residing within municipal effluent-dominated systems.

In vivo, platelets associate with neutrophils at sites of hemorrhage or inflammation. In vitro, stimulated platelets bind to neutrophils in a Ca2(+)-dependent manner. GMP-140, an integral membrane glycoprotein found in secretory granules of platelets and endothelium, is rapidly translocated to the cell surface after cellular activation. It shares sequence similarity with two leukocyte adhesion molecules, ELAM-1 and a lymphocyte homing receptor. We have recently shown that neutrophils bind to purified GMP-140 in a Ca2(+)-dependent fashion, and that GMP-140 participates in adhesion of neutrophils to activated endothelium. In this study we demonstrate that GMP-140 also mediates adhesion of neutrophils to stimulated platelets. Fixed thrombin-activated human platelets, but not unstimulated platelets, formed rosettes around neutrophils in the presence of Ca2+. The binding of platelets to neutrophils was inhibited by a monoclonal antibody to GMP-140 and by purified GMP-140. By promoting close cell-cell contact, GMP-140 may recruit both platelets and neutrophils to sites of tissue injury as well as modulate the function of each cell type by the other.

OBJECTIVE: The aim of this study was to extend previous examinations of aviation accidents to include specific aircrew, environmental, supervisory, and organizational factors associated with two types of commercial aviation (air carrier and commuter/ on-demand) accidents using the Human Factors Analysis and Classification System (HFACS). BACKGROUND: HFACS is a theoretically based tool for investigating and analyzing human error associated with accidents and incidents. Previous research has shown that HFACS can be reliably used to identify human factors trends associated with military and general aviation accidents. METHOD: Using data obtained from both the National Transportation Safety Board and the Federal Aviation Administration, 6 pilot-raters classified aircrew, supervisory, organizational, and environmental causal factors associated with 1020 commercial aviation accidents that occurred over a 13-year period. RESULTS: The majority of accident causal factors were attributed to aircrew and the environment, with decidedly fewer associated with supervisory and organizational causes. Comparisons were made between HFACS causal categories and traditional situational variables such as visual conditions, injury severity, and regional differences. CONCLUSION: These data will provide support for the continuation, modification, and/or development of interventions aimed at commercial aviation safety. APPLICATION: HFACS provides a tool for assessing human factors associated with accidents and incidents.

The Human Factors Analysis and Classification System (HFACS) is a general human error framework originally developed and tested within the U.S. military as a tool for investigating and analyzing the human causes of aviation accidents. Based upon Reason’s (1990) model of latent and active failures, HFACS addresses human error at all levels of the system, including the condition of aircrew and organizational factors. The purpose of the present study was to assess the utility of the HFACS framework as an error analysis and classification tool outside the military. Specifically, HFACS was applied to commercial aviation accident records maintained by the National Transportation Safety Board (NTSB). Using accidents that occurred between January 1990 and December 1996, it was demonstrated that HFACS reliably accommodated all human causal factors associated with the commercial accidents examined. In addition, the classification of data using HFACS highlighted several critical safety issues in need of intervention research. These results demonstrate that the HFACS framework can be a viable tool for use within the civil aviation arena.\n

During active intestinal inflammation polymorphonuclear leukocytes (PMN) transmigrate into the lumen and release 5'-AMP (J. Clin. Invest. 1993. 91:2320-2325). 5'-AMP is converted to adenosine by the apical epithelial surface with subsequent activation of electrogenic Cl- secretion (the basis of secretory diarrhea) via apical A2b adenosine receptors (J. Biol. Chem. 1995. 270:2387-2394). Using a polarized human intestinal epithelial monolayer (T84), we now characterize the basis of the observed conversion of 5'-AMP to adenosine required for this paracrine signaling pathway. An inhibitor of the ecto-5'-nucleotidase CD73, alpha, beta-methylene ADP (AOPCP), inhibited epithelial Cl- secretory responses to 5'-AMP, but not to authentic adenosine. Confocal immunofluorescent microscopy revealed CD73 to be surface expressed on both model and natural human intestinal epithelia. Expression was about sixfold greater on the apical cell surface as assessed biochemically by selective cell surface biotinylation, and morphologically by immunofluorescence. Treatment with phosphotidylinositol specific-phospholipase C (PI-PLC) released 95% of apical CD73, indicating that the intestinal CD73 possesses a glycosylphosphatidylinositol (GPI) anchor. Neither adenosine nor 5'-AMP stimulation induced intact T84 cells to shed surface CD73. The bulk of apical CD73 ( approximately 60%) was released from the cell surface by treatment with 1% Triton X-100 (TX-100) at 4 degrees C, but such release was not affected by pretreatment with ligand or by prior, antibody-mediated cross-linking of CD73. Subsequent analyses showed that the subpool of CD73 released by TX-100 at 4 degrees C was not truly solubilized, but rather represented TX-100-induced release of CD73-containing membrane fragments. These membrane fragments displayed light density on sucrose gradients characteristic of detergent insoluble glycosphingolipid-rich membrane domains (DIGs)/ caveolae, were solubilized by n-octyl glucoside (NOG, 1%) at 4 degrees C, and contained caveolin. These data indicate that human intestinal epithelia express CD73, which is apically polarized and targeted to microdomains with DIGs/caveolae characteristics. CD73 likely participates in translating paracrine, PMN-derived 5'-AMP signals to the authentic effector adenosine. These studies define CD73 as central to PMN-mediated intestinal Cl- secretion, the major directacting mechanism by which PMN induce intestinal epithelial Cl- secretion.

Physicians are often asked to provide assistance when symptoms develop in a passenger during a commercial flight. This Review Article identifies the most common problems that develop during air travel. The authors recommend ways to respond to such events and describe the resources that are available to physicians and flight crews while the aircraft is still airborne.

The present study examined the dimensionality and construct validity of the Perceptions of Organizational Politics Scale (POPS) which is comprised of three subscales: (1) General Political Behavior, (2) Going Along to Get Ahead, and (3) Pay and Promotion. Results of analyses conducted on data collected from 1,297 civilian government employees were inconsistent with a multidimensional factor structure of the POPS. Principal components and confirmatory factor analyses failed to confirm the Kacmar and Ferris 3-factor solution. Rather, the results indicated that the POPS was unidimensional. POPS scores were strongly and inversely related to scores on the Survey of Perceived Organizational Support (SPOS). POPS and SPOS scores were not differentially correlated with other job attitude measures.

Boredom and monotony are generally conceded to be negative factors that can have adverse effects on morale, performance, and quality of work. This article examines the evidence for yet another claimed effect of boredom and monotony, viz., that these factors are stressors, and that because they are stressors, they may produce effects even more detrimental than those mentioned above. Both laboratory and field studies are examined for evidence of increased neuroendocrine activity during exposure to conditions determined to be, or generally acknowledged to be, boring or monotonous. It is concluded that the available data offer no support for the belief that boredom or monotony per se produces the syndrome of stress. However, monotony coupled with a need to maintain high levels of alertness could represent a combination capable of eliciting considerable stress.

Approximately 6% of dog platelets are positive for staining with thiazole orange, a dye frequently used to stain ribonucleic acid. In this report, thiazole-orange positivity is shown to mark platelets that are less than 24 hours old. Dog platelets were derivatized in vivo with N-hydroxysuccinimido biotin such that greater than 95% of all platelets were biotinylated. Newly synthesized, nonbiotinylated platelets were then monitored by flow cytometry for their ability to bind thiazole orange. After biotinylation, the percentage of biotin-negative, thiazole-orange-positive platelets increased gradually from 0.72% at 30 minutes to 5.44% at 24 hours. These data indicate that thiazole-orange staining does label newly synthesized platelets.

The feasibility of a gradational step test for the assessment of work capacity was investigated. A device was constructed on which the level of a stepping platform could be raised between 2.0 and 50 cm as subjects continued work at a prescribed stepping rate. Two test procedures applicable to individuals who vary in their state of health from that of a chronically ill patient to a trained athlete are described. Sixty men performed experiments to establish the minute-by-minute metabolic costs of the work in the two tests. The oxygen expenditures ranged from 12.9 ± 1.2 to 40.8 ± 3.5 ml/min per kg in the 30/min step test and from 10.7 ± 1.1 to 28.8 ± 1.3 ml/min per kg in the 24/min step test. The procedures are well suited for measuring various physiological parameters during stepping and for establishing physiological working limits. The oxygen costs of the “negative” and “positive” work components in stepping were determined. The cost of negative work was approximately one-third of the positive work. An equation was derived for predicting the metabolic costs of stepping at various rates and platform levels. Comparisons of predicted and measured oxygen intake values for the 30-step and 24-step tests approximated one another at all levels of energy expenditure. energy expenditure stepping; cardiorespiratory responses to exercise; work in stepping; negative work; positive work; physical fitness tests Submitted on August 7, 1964

BACKGROUND: We studied the complications of peripheral intravenous (i.v.) catheters in the hand and forearm in a teaching hospital over a 3-year period. METHODS: The records of 67 patients who developed i.v. catheter-related complications were reviewed. RESULTS: The most common sites for developing complications in order of frequency were the forearm, hand, wrist, and antecubital fossa. There were 56 minor and 11 major complications. More than 50% of minor complications occurred in the hand and wrist, and more than 50% of major complications occurred in the hand. In 68% of minor complications, the patients were aged 50 years or older and 68% were women. Minor complications comprised 26 intravenous infiltrations, 23 cases of thrombophlebitis, and 7 cases of cellulitis. Ninety percent of major complication patients were aged 50 or older and 82% were women. Major complications included septic thrombophlebitis in three; hematomas resulting in skin necrosis in two; and infiltration related complications in six, resulting in skin necrosis in two, compressive nerve lesions in two, digital stiffness in one, and compartment syndrome in one. Ten patients with major complications were over the age of 50 years and nine were women. Two patients receiving anticoagulation developed large dorsal subcutaneous space hematomas. Chemotherapeutic agents contributed to two minor complications and one major complication. CONCLUSION: The hand is a common site for minor and major i.v. catheter complications. Women and older patients are more susceptible to these complications. Peripheral i.v. line complications are not uncommon and can result in morbidity and increased health care costs from prolonged hospitalization, extended use of i.v. antibiotic therapy, and surgical intervention.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

Clinicians who care for patients infected with coronavirus disease 2019 (COVID-19) must wear a full suite of personal protective equipment, including an N95 mask or powered air purifying respirator, eye protection, a fluid-impermeable gown, and gloves. This combination of personal protective equipment may cause increased work of breathing, reduced field of vision, muffled speech, difficulty hearing, and heat stress. These effects are not caused by individual weakness; they are normal and expected reactions that any person will have when exposed to an unusual environment. The physiologic and psychologic challenges imposed by personal protective equipment may have multiple causes, but immediate countermeasures and long-term mitigation strategies can help to improve a clinician's ability to provide care. Ultimately, a systematic approach to the design and integration of personal protective equipment is needed to improve the safety of patients and clinicians.

The present study examined the hypothesis that procedural justice and distributive justice are positively related. In other words, when individuals perceive fairness in how decisions are made, they are likely to perceive the outcomes as fair. Similarly, when individuals perceive a fair outcome, they are likely to believe that fair procedures led to that outcome. In line with the Tyler group-value model of procedural justice, it was hypothesized that this would hold true primarily when the individual has a long-term view of organization membership, a view influenced by the individual's disposition to delay gratification or reward. Hierarchical-moderated multiple regression analyses on data collected from workers in a small American tooling plant supported this hypothesis. These results have implications for attempts to enhance perceptions of justice.

A serial‐reaction task was used to study personality, as well as physiological, correlates of individual differences in performance decrement under low task‐load conditions. Sixty subjects performed the task continuously for 40 min. Extraverted subjects showed increasing lapses of attention, while introverted subjects failed to show any evidence of a decline in attention. Of the two extraversion components (impulsivity and sociability), impulsivity was the component responsible for the obtained decrement. Heart‐rate variability showed significant relationships with personality and with performance decrement, while mean heart rate did not.

Six subjects were given a series of 10 rotary trials in which accelerations of 1.0d`/sec2 and 1.8d`/sec2 were employed for durations of 84 and 50 seconds respectively. Subjective states of arousal were manipulated by instructions. Duration and slow-phase velocity of nystagmus were measured. Qualitative as well as quantitative differences were observed as a function of arousal level.Results indicated: (1) during mentally active states, no decline of nystagmus was evident during stimulation nor was there an abrupt cessation of nystagmus accompanying stimulus termination; (2) during states of mental relaxation, the nystagmic response was reduced, declines during stimulation appeared, and the response occasionally ended prior to, or at the moment of, stimulus termination.Theoretical implications of the findings are discussed.

Eleven private pilots (seven men and four women) were recruited and trained on the Multiple Task Performance Battery (MTPB), static and dynamic tracking of a localizer/glide slope instrument, and use of the Intoxilyzer. The experiment comprised four test sessions (vodka, bourbon, placebo, and control sessions) held at weekly intervals. Sessions began at about 5:00 p.m. and continued through midnight to about 11:00 a.m. the next day. Subjects were tested in groups of three or four and were not told whether they were drinking alcohol or placebo. The ordering of sessions was approximately counterbalanced. Subjects were given all tests in the evening (before and after a monitored dinner), drank prepared beverages from 8:30 p.m. to midnight, and were tested again. Subjects slept 4 to 5 hr. They were awakened around 7:00 a.m., fed, and asked to perform all tasks again, beginning at 8:00 a.m. (8 hr after they had finished drinking). Results showed clear deleterious effects of alcohol on the MTPB and the tracking tasks immediately following drinking. During the morning (hangover) tests, scores on the MTPB and on the static and dynamic tracking tasks showed small circadian effects (scores were better) without impairment due to the alcohol. There were no congener effects. These results offer no evidence contrary to the "8 hour rule."

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. METHOD: Adult subjects (N = 2229; 56.2% male) aged 18-69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA-PGC PTSD sites underwent T1-weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel-wise (brainageR) and region-of-interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age - chronological age) controlling for chronological age, sex, and scan site. RESULTS: BrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three-way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages. DISCUSSION: Differential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age-related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan.

The present study examined the relationships between reported importance of participation in decision making and three job attitudes of relevance to Yugoslav self-management, namely job satisfaction, perceptions of organizational support, and perceptions of organizational goal norms. Data collected from 134 of 200 randomly sampled workers in a Yugoslav tooling plant yielded weak correlations but also indicated a moderating effect of exchange ideology. These results have implications not only for Yugoslav self-management but also for exchange theory and the study of job attitudes.